ES2389945T3 - Subdermal cryogenic remodeling of muscles, nerves, connective tissue, and / or adipose tissue (fat) - Google Patents

Abstract

A system for cosmetically restoring an exposed skin surface of a patient, the system comprising: a body having at least one patch of cooling fluid supply (23), in which the body comprises a handpiece (42); a probe (26) that is in thermal communication with said cooling fluid supply patch and that extends distally from the body, the probe comprising a probe body (158, 170, 174) that includes a matrix of tissue penetrating needles ( 54), each needle extending distally from the probe body and comprising a sharp, sealed or blocked distal end inserted into a patient's target tissue across the skin surface; wherein the inner light of the respective needle is configured to receive a cooling fluid from the outlet (70) of a cooling fluid light (58) disposed inside the handpiece (42); a source of fluid of cooling (48) coupled to the at least one patch of cooling fluid supply (23) of the body to cool the tissue penetrating needles (54) distally of the body of the probe in order to remodel adjacent tissue and temporarily inhibit the contraction of a subdermal muscle and reduce the appearance of wrinkles and grooves on the side associated with muscle contraction; and, proximally of the distal ends of the needles (54), an applicator (62, 118) of the probe to apply energy or material in order to inhibit the injury induced by cooling along the surface of the skin.

Description

Cryogenic subdermal remodeling of muscles, nerves, connective tissue, and / or adipose tissue (fat).

BACKGROUND OF THE INVENTION

[0001] The present invention is generally directed to medical devices and systems, particularly to improve the appearance of a patient and other applications. Embodiments of the invention include devices and systems for applying cryogenic energy to subcutaneous tissues such that they selectively reshape one or more target tissues below an exposed skin surface inhibiting undesirable and / or unsightly effects of the skin (such as , wrinkles, grooves, or cellulite dimples) or in other surrounding tissues. The remodeling of the target tissue can achieve a desired change in its behavior or composition, and will often help alleviate the cosmetically undesirable characteristics.

[0002] The desire to restore various features of the human body is common both to correct a deformity and merely to enhance personal appearance. This is evidenced by the growth in the volume of cosmetic surgery procedures performed annually, see document US2002 / 0120260 A1.

[0003] Many procedures are planned to alter the superficial appearance of the skin by reducing wrinkles and furrows. Some of these procedures involve injecting fillers or stimulating the production of collagen. More recently, drug-based therapies for groove correction and other cosmetic applications are increasingly popular.

[0004] Botulinum toxin type A (BOTOX®) is an example of a drug-based therapy used in cosmetic applications. It is normally injected into the facial muscles to block muscle contraction, resulting in innervation or temporary paralysis of the muscle. Once the muscle is disabled, the movement that contributes to the formation of the undesirable groove is temporarily eliminated. Another example of pharmaceutical cosmetic treatment is mesotherapy, in which a cocktail of homeopathic medication, vitamins, and / or drugs approved for other indications in the skin is injected to administer the healing or corrective treatment to a specific area of the body. Various cocktails are planned to carry out body sculpting and cellulite reduction by dissolving adipose tissue, or rejuvenating the skin by enhancing collagen. The development of non-drug-based cosmetic treatments also continues. For example, endermology is a mechanics-based therapy that uses vacuum suction to stretch or loosen fibrous connective tissues that are involved in the appearance of cellulite dimples.

[0005] Although BOTOX® and / or mesotherapies can temporarily reduce wrinkles and grooves, reduce fat, or provide other cosmetic benefits, they are not without problems, particularly the dangers associated with the injection of a known toxic substance into a patient, the potential dangers of injecting unknown and / or unproven cocktails, and the like. Additionally, although the effects of endermology are not considered potentially dangerous, they are of short and / or medium duration.

[0006] In light of the foregoing, it would be desirable to provide improved medical devices, systems, and procedures, particularly for the treatment of grooves, fat, cellulite, and other cosmetic defects. It would be particularly desirable that these new techniques provide an alternative mechanism for improving visual appearance that could replace and / or complete known bioactive and other cosmetic therapies, ideally allowing patients to decrease or eliminate the injection of harmful toxins and cocktails by providing You see similar or improved cosmetic results. It would also be desirable for such techniques to be performed percutaneously using only local anesthesia or no anesthesia without cuts or with a minimal cut of the skin, without the need for sutures or other closure procedures, without extensive bandage and with limited appearance of bruises or no bruising or other factors that contribute to an extensive recovery of the patient or "downtime" of a patient.

BRIEF SUMMARY OF THE INVENTION

[0007] The present invention is defined in the appended claims. Improved medical devices, systems, and procedures that are not part of the invention or the treatment of cosmetic defects and other applications are described. In the examples described, cold is applied with at least one probe inserted through an exposed surface of a patient's skin. The cooling can reshape one or more target tissues in such a way as to effect a desired change in a composition of the target tissue and / or a change in its behavior. Exemplary cooling treatments will interfere with the nerve / muscle contractile function chain with the aim of mitigating the furrows, and related treatments can be used therapeutically to treat muscle spasms of the back and other muscles. , chronic pain, and the like. Some may reshape the subcutaneous adipose tissue or fibrous connective tissue in such a way that they alter the shape or appearance of the skin's surface.

[0008] Optionally, cooling times, temperatures, pressures, vaporization of the cooling fluid or the like can be configured to provide a desired or selectable efficacy time variable. Treatments at moderate temperatures (for example, at temperatures that only temporarily atrophy the tissues but do not induce significant apoptosis or necrosis) can only have short-term muscle contraction inhibition effects. Other treatments may be more durable, being optionally permanent. Efficacy based on the fibroblastic response may, in some examples, be self-limiting. The designs of the probe, the applicator, and / or the controller can allow the application of the treatment by people with limited experience and practice, so that the effectiveness is not dependent on the operator. In some examples, foreign bodies and / or materials are not left behind. Other examples may employ materials such as bioactive substances, a warm saline solution, or the like to limit the lesion and / or increase the effectiveness of remodeling, some treatments being combined with pharmaceutical compounds such as BOTOX® or the like. Similarly, it will not be necessary to remove tissue to achieve the desired effect in many embodiments. Advantageously, the cooling probe, a single-use cooling fluid cartridge can be included, and the controller can be incorporated into a disposable (often non-sterilizable) self-contained treatment system that can limit capital investment and facilitate treatments in third world environments.

[0009] A procedure for improving the cosmetic appearance of a patient is described. The patient has a skin surface, and the procedure comprises inserting a probe through the skin surface and cooling a target tissue below the skin surface so that the target tissue is remodeled. The remodeling of the target tissue alters a shape of the skin's surface.

[0010] In many cases, before remodeling, superficial skin will show wrinkles or furrows. The contraction of the subdermal muscles and the associated movement of the skin can contribute to the development and appearance of these wrinkles or furrows, and the remodeling can be carried out in such a way as to reduce or eliminate this contraction and / or movement, softening Effectively wrinkles or furrows. The skin surface will often include a region of the face, the target tissues optionally comprising a muscle, a nerve, connective tissue, a nerve / muscle junction, and / or the like associated with this muscle. Cooling can inhibit muscle contraction in a way that improves the patient's appearance.

[0011] In many examples, a lesion induced by cooling the surface of the skin can be inhibited such that the target tissue is cooled selectively. For example, thermal energy can be applied along the skin surface, optionally heating the skin surface with a probe applicator, before, during, and / or after cooling of the target tissue. A material that inhibits cooling injury along the surface of the skin during cooling may also be provided, such as a heated biocompatible fluid, a biocompatible cryoprotectant (optionally comprising dimethylsulfoxide ("DMSO"), propylene glycol, and / or glycerol). In some embodiments, the lesion on the surface of the skin can be inhibited by applying a material that enhances the injury by cooling on the target tissue such that cooling and overall damage to the skin can be limited. It will often be desirable to limit the lesion to the skin surface sufficiently to avoid permanently altering the color of the skin surface, and / or limit or prevent visible necrosis of the dermal tissues along the skin surface.

[0012] In some examples, the skin surface may have irregular cellulite or other texture and / or shape induced by adipose tissue. The remodeling can be carried out in order to soften said texture to improve the patient's appearance. Optionally, cooling can be carried out in order to induce a reduction in tissue mass after removal of the probe from the patient. The reduction in tissue mass can be reduced as part of a tissue response to cooling, optionally as part of the healing process, and the reduction in tissue mass can at least help provide a desired change in surface shape. of the skin For example, when the tissue comprises an adipose tissue, the healing response to cooling can decrease the mass of adipose tissue inducing the restoration of adipose tissue. In other examples, cooling may reduce muscle mass, particularly of the muscles of the face that are associated with wrinkles and grooves.

[0013] In general, the target tissue can be cooled to a temperature of about 10 ° C to about -40 ° C, the target tissue is optionally cooled to a temperature in the range of about 0 ° C to about -15 ° C. Moderate (for example, hotter than about -5 ° C) and shorter treatment times may provide temporary efficacy, although cooler treatment temperatures (for example, at about -5 ° C or colder) and longer treatment times may result in permanent changes in the target tissue and in the shape of the skin surface. Surprisingly, for some treatment temperature ranges, hotter treatments can provide long-term and even permanent efficacy, while cooler treatment temperatures can result in temporary changes in the target tissue and surface shape of the treatment. skin. For example, in some examples, long-term or permanent efficacy can be provided by apoptosis (sometimes referred to as programmed cell death). In contrast, effects based on necrosis can be reduced or eliminated with scarring. Apoptosis can reduce muscle mass or disrupt the contractability chain without inducing inflammation and stimulating satellite cells that may be involved in the skeletal muscle repair process. Alternative mechanisms may also be involved, including temporary and / or permanent loss of elasticity in muscle tissues due to changes in the morphology of collagen and / or elastin with ice formation, necrosis, a loss of elasticity in connective tissue. fibrous, impaired signal transmission along the neural pathways, blocking the production of acetylcholine (or other chemicals relevant for contractability) or disrupting conductivity, hypoxia (optionally cutting off the blood supply to a muscle or other tissue in the contractile chain by apoptosis or some other mechanism), or the like.

[0014] Advantageously, a permanent or temporary effect can be selected, even if the duration of the effect is optionally selected by the patient and / or the user of the system, which allows (for example) an initially temporary treatment to be carried out carried out in such a way that it is verified if the results are the desired ones before implementing a lasting or permanent treatment. In some examples, smaller doses or regions of a more permanent effect can be administered sequentially over time in order to achieve a desired permanent full effect while avoiding drastic overdosing, or undesirable results.

[0015] In many examples, a plurality of tissue penetrating probes can be inserted through the skin surface. Optionally, a separation between adjacent probes can be established such that the cooling effect remodels a desired portion, most of, substantially all of, and / or all tissues disposed between the probes. Differentiated amounts of tissue and / or target tissue models can provide different desired effects, optionally treating the target tissues in sequence using a single tissue penetrating probe or the like.

[0016] A procedure for improving the cosmetic appearance of a patient is described. The patient has a skin surface with a muscle underneath. The muscle has an associated nerve / muscle contractile chain. The chain normally includes, for example, muscle, a nerve, a connective tissue (such as a ligament, tendon, cartilage, or the like), and / or a nerve / muscle junction, and may also encompass related tissues such as vessels. blood supplying blood to the muscles or the like. The procedure comprises directing the energy

or cooling from a probe to a component of the contractile chain of the nerve / muscle in such a way that the component is remodeled and remodeling inhibits muscle contraction in order to improve the cosmetic appearance of the skin surface.

[0017] A procedure for improving the cosmetic appearance of the patient is described. The patient has a skin surface with a tissue underneath. The tissue has a mass, and the method comprises directing sufficient energy of tissue remodeling or cooling of a probe through the surface of the skin to induce a reduction in tissue mass such that the cosmetic appearance is improved. of the skin surface.

[0018] A procedure for treating a patient is described. The patient has a skin surface and a muscle below. The method comprises directing sufficient energy or cooling of tissue remodeling below the surface of the skin such that muscle contraction is inhibited or a loss of elasticity is induced. Related procedures may comprise applying chemical substances, and / or a means of cutting the blood supply of tissue.

[0019] In conjunction with directing cooling towards (for example) a component of the contractile chain of a muscle, at least some of a variety of forms of energy transmissions to these or other tissues can be relied on in order to inhibit muscle contraction, decrease muscle mass (or other tissue), and the like. Suitable forms of energy that may be used in place of or in conjunction with cooling may include ultrasonic energy, radiofrequency electrosurgical energy, microwave energy, laser energy, electromagnetic or particle radiation, and the like. Optionally, any of these treatment modalities can be combined with the use of bioactive substances, chemical substances or a method of cutting the blood supply to the tissue.

[0020] A system for cosmetically restoring an exposed skin surface of a patient is described. The system comprises a probe body that has at least one patch of cooling fluid supply. At least one tissue penetrating probe extends distally from the body. The at least one probe has an end that pierces the distal tissue and is in thermal communication with at least one patch of cooling fluid supply. A source of cooling fluid is coupled to at least one patch of cooling fluid supply in order to cool the at least one probe distally of the body. Cooling can reshape adjacent tissue when at least one probe is inserted through the skin's surface, and remodeling can restore the skin's surface.

[0021] In many examples, a controller will be attached to the cooling fluid patch in order to control the treatment time and / or the treatment temperature. The controller may have an input to identify the desired duration of the remodeling, and the controller may determine a cooling characteristic in response to the desired duration.

[0022] In some examples, a cooling region of the probe or probes inserted through the skin surface may have a cooling region to selectively cool the target tissue, the cooling region optionally separating from the proximal end of the probe. insertable For example, an isolated region can be extended between the cooling region and the surface of the probe that is implanted in the skin or any of a variety of other collateral tissues can be protected. The materials and / or energy can be directed to the tissues along the surface of the skin, or one or a variety of other collateral tissues can be protected.

[0023] A system for improving the cosmetic appearance of a patient is described. The patient has a skin surface with a tissue underneath. The tissue has a mass, and the system comprises a probe that has a surface that is implanted in the tissue that directs sufficient tissue remodeling energy or cooling from the probe through the skin surface to induce a reduction in tissue mass in such a way that the cosmetic appearance of the skin surface is improved.

[0024] A system for treating a patient is described. The patient has a skin surface, and a muscle below. The system comprises a transmission surface that directs sufficient energy or cooling of tissue remodeling below the surface of the skin such that muscle contraction is inhibited.

BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Fig. 1A is a perspective view of a self-contained subdermal cryogenic remodeling probe and system, in accordance with an embodiment of the invention.

[0026] Fig. 1B is a partially transparent perspective view of the self-contained probe of Fig. 1A, showing the internal components of the cryogenic remodeling system.

[0027] Figs. 2 and 2A-2L illustrate the target tissues for treatment in some embodiments of the present invention, together with the associated wrinkles or grooves and treatment models.

[0028] Fig. 2M is a functional block diagram that graphically illustrates the tissue components included in a contractile chain.

[0029] Fig. 3 is a block diagram schematically illustrating the functional components of the self-contained probe of Fig. 1A.

[0030] Fig. 3A is a perspective view schematically illustrating another embodiment of a subdermal cryogenic remodeling system having a handpiece of the distal probe coupled to a proximal housing by a flexible body.

[0031] Fig. 3B is a side view schematically illustrating a distal handpiece of the system of Fig. 3A, showing a probe body with a plurality of tissue penetrating probes extending from the foregoing.

[0032] Fig. 3C is a cross-sectional view showing the structure of the tissue penetrating probes of the probe body of Fig. 3B.

[0033] Fig. 4A is a cross-sectional view of an alternative tissue penetrating probe that has insulation along the proximal portion of the probe in order to inhibit adjacent cooling in the probe body.

[0034] Fig. 4B is a cross-sectional view further showing a cryogenic probe penetrating the alternative tissue having an opening at the distal end, together with the method for its use.

[0035] Figs. 5A and 5B schematically illustrate cross-sectional views of a handpiece of the alternative treatment probe having a plurality of tissue penetrating cooling probes, and also having an applicator for applying energy and / or an injectable material to inhibit the cooling lesion between the target tissues and the skin surface.

[0036] Figs. 6A and 6B graphically illustrate the temperature distributions measured from a centerline of a tissue penetrating cryogenic cooling probe.

[0037] Figs. 7A and 7B are perspective views schematically illustrating a proximal housing and a distal handle of another subdermal cryogenic remodeling system, respectively.

[0038] Figs. 8A-8C illustrate a plurality of alternative treatment handpieces having a variety of different matrices of the tissue penetrating cooling probe.

[0039] Fig. 9 is a flowchart that schematically illustrates a procedure for cosmetically treating in target tissue disposed below the surface of the skin using cryogenic cooling in order to restore the surface of the skin.

DETAILED DESCRIPTION OF THE INVENTION

[0040] The present invention provides improved medical devices, a system and procedures. Embodiments of the invention will facilitate the remodeling of tissues arranged below the skin, often in order to alter the shape of the surface of the skin that is above, while inhibiting or preventing collateral skin lesion. and the formation of associated skin scars, discoloration, and the like.

[0041] Among the most immediate applications of the procedure may be the improvement of wrinkles and grooves, particularly, inhibiting the muscle contractions that are associated with these cosmetic defects in order to improve the patient's appearance Rather than completely relying on a Pharmacological toxin or the like to disable muscles in order to induce temporary paralysis, many embodiments of the invention will use cold at least in part to immobilize the muscles. Advantageously, the nerves, muscles, and associated tissues can be temporarily immobilized using moderately cold temperatures of 10 ° C to -5 ° C without permanently disabling tissue structures. Using a solution similar to that used to identify the structures associated with atrial fibrillation, a needle probe or other treatment device can be used to identify a target tissue structure in a diagnostic mode with these moderate temperatures, and the same probe ( or a different probe) can also be used to provide long-term or permanent treatment, optionally removing the target tissue area and / or inducing apoptosis at temperatures of about -5 ° C to about -50 ° C. In some embodiments, it can induce apoptosis using treatment temperatures of about -1 ° C to about -15 ° C, optionally, in order to provide a permanent treatment that limits or prevents inflammation and mobilization of the repair of satellite cells of skeletal musculature. In this way, the duration of the treatment efficacy of said subdermal cryogenic treatments can be selected and controlled, with cooler temperatures, longer treatment times, and / or larger volumes or selected target tissue models that determine the longevity of the treatment.

[0042] In addition to cosmetic treatments for wrinkles, grooves, and the like, embodiments of the invention may also find applications for pain relief, including those associated with muscle spasms. Additionally the embodiments may depend on the application of energy (with or without cooling) for the remodeling of target tissues and the production of a desired cosmetic effect, the energy optionally comprising focused or non-focused ultrasound energy, radiofrequency energy, laser energy, microwave energy, other electromagnetic or particle radiation, alternative procedures for applying heat, chemicals, vascular embolization, and the like. In this way, a variety of embodiments can be provided.

[0043] Referring now to Figs. 1A and 1B, a system for subdermal cryogenic remodeling that is not part of the invention comprises a handpiece of the self-contained probe having a proximal end 12 and a distal end 14. A housing of the handpiece 16 has a size and a suitable way to hold in the hand of a surgeon or other system operator. As can be seen more clearly in Fig. 1B, a cryogenic cooling fluid supply 18 and a source of electrical energy 20 are located inside the housing 16 together with a circuit 22 having a processor to control the applied cooling. by means of a self-contained system 10 in response to the performance of an input 24.

[0044] Extending distally from the distal end 14 of the housing 16 is a tissue penetrating cryogenic cooling probe 26. The probe 26 is thermally coupled to a patch of cooling fluid from a source of cooling fluid 18, the illustrative probe comprising a tubular body that receives at least a portion of the cooling fluid from the source of the previous cooling fluid. Illustrative probe 26 comprises a needle 30 g having a sharp distal end that is axially sealed. The probe 26 may have an axial length between the distal end 14 of the housing 16 and the distal end of the needle between about 1/2 mm and 5 cm, preferably having a length of about 1 mm to about 3 mm. Such needles may comprise a stainless steel tube with an internal diameter of approximately 0.006 inches (0.015 cm) and an external diameter of approximately 0.012 inches (0.030 cm), while alternative waves may comprise structures having external diameters (or other dimensions). lateral cross section) from about 0.006 inches (0.015 cm) to about 0.100 inches (0.254 cm).

[0045] With respect to any of the components inside the housing 16, the exemplary cooling fluid supply 18 comprises a cartridge containing a pressurized liquid, the liquid preferably having a boiling temperature of less than 37 ° C. When the fluid is thermally coupled to the tissue penetrating probe 26, and the probe is placed inside the patient such that the external surface of the probe is adjacent to a target tissue, heat from the target tissue evaporates at least a portion of the liquid and the enthalpy of vaporization cools the target tissue. A valve (not shown) may be arranged along the cooling fluid flow patch between the cartridge 18 and the probe 26, or along the cooling fluid patch after the probe in order to limit the temperature , the time the temperature change rate, or other cooling characteristics. The valve will always be electrically powered by a power supply 20, according to the address of the processor 22. The exemplary power supply 20 comprises a rechargeable or single use battery.

[0046] The exemplary cooling fluid supply 18 comprises a single use cartridge. Advantageously, the cartridge and the cooling fluid of the former can be stored and / or used at room temperature (or even above). The cartridges may have a fragile seal or may be refillable, the example cartridge containing liquid N2O. A variety of alternative cooling fluids, exemplary cooling fluids that include fluorocarbon and / or carbon dioxide refrigerants, can also be used. The amount of cooling fluid contained in the cartridge 18 will normally be sufficient to treat at least one significant region of a patient, but will often be less than sufficient to treat two or more patients. An exemplary liquid N2O cartridge may contain, for example, an amount in a range of about 7 g to about 30 g of liquid.

[0047] The processor 22 will typically comprise a programmable electronic microprocessor that incorporates a computer code reader or programming instruction set to implement one or more of the treatment procedures described herein. The microprocessor will typically include or be coupled to a memory (such as a non-volatile memory, a flash memory, a read-only memory ("ROM"), a random access memory ("RAM"), or the like) that stores computer codes and data for use in this way, and / or recording means (including magnetic recording means such as a hard disk, a floppy disk, or the like) may be provided; or optical recording media such as a CD

or DVD). Suitable interface devices (such as digital to analog or analog to digital converters, or the like) and input / output devices (such as USB or serial I / O ports, wireless communication cards, graphic display cards can also be provided) , and the like). A wide variety of commercially available or specialized processor structures can be used in the different embodiments, and suitable processors can make use of a wide variety of hardware combinations and / or hardware / software combinations. For example, the processor 22 may be integrated into a single processor board and may operate with a single program or may use a plurality of boards operating with numerous different program modules in a wide variety of data processing or distributed code architectures of alternative way.

[0048] Referring now to Figs. 2 to 2M, the subdermal cryogenic remodeling of tissues as a palliative for wrinkles and grooves will find specific applications in the surface regions of the skin of the face and neck, optionally carrying out procedures in order to alter the function Contractile of the AI muscles in the upper third of the face as shown in Fig. 2. Treatments can be carried out to alleviate in this way frown lines, wrinkles or furrows between the eyes, crow's feet , horizontal wrinkles on the forehead, neck, grooves around the mouth, chin, and the like. Many of these cosmetic defects can be treated by directing and / or inactivating tissues such as corrugator and / or procerus muscles. More specifically, as seen in Figs. 2A and 2B, the movement of the facial muscles can cause the skin to wrinkle, for example, by contraction of the corrugator muscle J and / or the procerus K muscle that leads to wrinkles between the eyebrows L, which can be referred to clinically like glabellar wrinkles. Additional treatment locations, M-Q muscles whose contractile function can be directed, wrinkles or related grooves, and R treatment models are illustrated in figs. 2C-2L.

[0049] With respect to the specific muscles and tissue structures identified in Fig. 2, treatments can be directed to one or more of the upper eyelid lift muscle A, the eye orbicular muscle B, the frontal muscle C , the lifting muscle of the lips D, the corrugator muscle E, the minor zygomatic muscle F, the major zygomatic muscle G, the buccinator muscle H, and the temporal muscle I. The treatments that direct the contraction of the oticularis muscle M of Fig. 2C can help decrease the furrows of the crow's feet of Fig. 2H, optionally using a treatment model R. Treatments that alter the function of the frontal muscle N of Fig. 2D can alleviate the grooves of Fig. 2L, while altering the functioning of the orbicular muscle O of Fig. 2E can relieve the grooves shown in Fig. 2J. Chin grooves can be mitigated as shown in Fig. 2K by treatment of the chin Tassel muscle P and neck grooves such as those in Fig. 2L can be improved by treatments of platysma Q muscle, such as seen in Fig. 2G. The R treatment models for the improvement of these and other cosmetic defects may correspond to or derive from known treatments (such as models for BOTOX® injections or the like) can be determined by anatomical analysis using the desired physiological effects, by animal studies or clinical, or similar.

[0050] The target muscles for the inhibition of contraction in order to alleviate the grooves and the like can often include the glabelar and procerus complex including, but not limited to, the corrugator and procerus muscles, the eye orbicular muscle, the depressor muscle, superciliary muscle, and frontal muscle. Other groups of muscles of the facial region can also be inhibited by contraction, such as the nasal muscle, the orbicularis muscle of the lips, the buccinator muscle, the triangular muscle of the lips, the upper and lower lip lifting muscle, the zygomatic muscle, jaws, the platysma muscle, the chin tassel muscle. The contraction of these and / or other muscles can be inhibited by directing the associated nerve tissues, connective tissues, the nerve / muscle interface, the blood supply, and / or at least a portion of tissues from one or more of these own muscles. Preferred groove relief treatments may alter the functioning of the muscles including one or more of, but not limited to the central part of the frontal muscle, the lateral part of the frontal muscle, the superciliary corrugator muscle, the procerus muscle, the muscle superciliary depressor, upper eyelid lift muscle, the orbital part the orbicularis eye muscle, the eyelid part of the orbicularis muscle of the eye, the upper lip and nose wing lift muscle, the upper lip lift muscle, the muscle minor zygomatic, the major zygomatic muscle, the triangular lifting muscle of the lips (aka caninus), the triangular depressor muscle of the lips (aka triangularis), the depressor muscle of the lower lip, the tassel muscle of the chin, the incisive muscle of the lip upper, the incisive muscle of the lower lip, the risorio muscle, the platysma muscle, the orbicularis muscle of the lips, the m masseter muscle, the temporalis muscle, the medial pterygoid muscle, the digastric muscle, the nasalis, the levator labii superioris and lower.

[0051] In many embodiments, remodeling of a tissue included in a contractile function chain 30 will effect a desired change in a composition of the treated tissue and / or a change in its behavior that is sufficient to mitigate the furrows associated with the contraction of a muscle 32, as illustrated in Fig. 2M. Although this may involve a treatment of muscle tissues 32 directly, treatments can also target nerve tissues 34, neuromuscular junction tissues 36, connective tissues 38, and the like. More additional tissues can be directly treated, for example, by targeting the tissues of selected blood vessels in order to induce hypoxia in the muscle or the like. With respect to the specific component of the contractile chain 30 that is treated, the treatment will preferably inhibit the contraction of the muscle 32 that would otherwise form grooves or wrinkles on the surface of the exposed skin lining this muscle.

[0052] A variety of tissue-specific remodeling treatment mechanisms that direct one or more components of the contractile chain 30 can be employed in order to inhibit wrinkles or furrows. For example, the removal of muscle cells / tissues, or associated nerves (optionally being an integral component thereof of nerve function such as a myelin sheath or similar), or nerve endings or neuromuscular junction (which In general, the interface between nerves and muscles) may be sufficient to inhibit muscle contraction. Such removal may result in short-term, long-term or permanent muscle inactivation. Other long-term or permanent treatments may involve induction of apoptosis, usually at temperatures that are not as severe as excision temperatures, but that reshape tissue behavior with long-term changes in cell life and / or in the cycles of proliferation. The specific remodeling mechanisms for the purpose of changing muscle function in a desired manner or for a desired time can be induced by appropriate therapeutic dosages of the treatment modalities described herein, for example, in order to induce the cell death (apoptotic or necrotic), embolization of the blood supply, or the like. Alternative remodeling mechanisms that may be shorter in effect may include stunning of one or more components of the contractile chain 30, inactivation of one or more components, or the like. Remodeling treatments that effectively block the release of or response to chemicals (such as, but not limited to acetylcholine) along the contractile chain 30 may be sufficient to inhibit muscle contraction in response to signals transmitted to along the neural pathways, both temporarily and permanently, and can also be used.

[0053] Muscle movement is generally controlled by nerve stimulation. The motor unit of the neuromuscular system contains three components; motor neuron (vertebral), axon (vertebral to motor terminal plate), and innervated muscle fibers (terminal plate to muscle): Treatments directed at one or more of these tissues can be used.

[0054] When treatments are intended to inhibit muscle contraction, treatment can be determined at least in part by the type of muscle being treated (skeletal (striated) or smooth (non-striated)). For example, skeletal muscle may have muscle fibers that are innervated by motor neurons, with a single neuromuscular junction that is found along the midpoint of muscle fibers, and a single muscle fiber within a motor unit served by a only motor neuron and its axon. Each muscle receives one or more service nerves, and the nerve usually enters deep into the surface of the muscle near its origin where the muscle is relatively immobile. Typically, some blood vessels accompany the nerve that enters the muscle into the neurovascular thread. Each nerve contains motor and sensory fibers, motor end plates, vascular smooth muscle cells, and various sensory endings and fascia endings. When the nerve is introduced into the muscle, it separates into a plexus that advances in the different layers of the muscle - epimisio, perimysium, endomysium - terminating each in different branches that bind to a muscle fiber in the motor terminal plate. The remodeling of one or more of these tissues may be sufficient to temporarily or permanently inhibit muscle contraction.

[0055] Embodiments of the invention can interrupt or disable nerve impulses by disrupting conductivity by eliminating or decreasing load differences across plasma membranes, both mechanically and chemically; destroying Schwann cells that isolate axonal processes accelerating impulse conduction; and / or by repeated repeated cycles of injury / scarring of limited capacity for neuronal regeneration.

[0056] Muscle immobilization can also be activated by disabling any one of a specified combination of the connective tissue matrix, both temporarily and permanently. Treatments aimed at connective tissues, such as fibroblasts, myofibroblasts (which may be responsible for the contractibility of granulation tissue in scarring), collagen, reticulin, or the like of aponeurotic or tendon junction of muscles to bone, fascia , ligaments, or the like can also be advantageous, and the shape of the remodeling and / or the dosage of the treatment can be selected in response to the ailment being treated (for example, when cellulite dimples are mainly treated rather which mainly treat wrinkles or grooves induced by contraction) Treatments of the superficial fascia just below the skin can also be used. To achieve a loss of elasticity in the fibrous connective tissue during cellulite treatment, the temperature can be varied to achieve temporary or permanent changes in the morphology of the collagen and elastin matrix contained within this tissue.

[0057] Together with the treatment of the target tissue using the probe 26, it will often be desirable to inhibit the lesion of the collateral tissues that are and are adjacent to the target tissues, and particularly of the tissues along the surface of the skin above target tissues. The lesion in any desired tissue (blood vessels, nerves, etc.) can be inhibited, particularly if it is determined that this tissue is not the goal of a particular therapy. As illustrated in Figs. 1A and 1B a distally oriented applicator 28 adjacent at the distal end 14 of the housing 16 may apply energy and / or material along the probe adjacent to the skin surface 26 in order to protect the surface tissues from the temperatures of treatment. The applicator 28 can, for example, be oriented to implant into tissues along the skin surface when the probe is inserted therethrough, the applicator heats the skin surface to avoid injury from the cooling probe. Heating can be provided by a resistive heater or the like, and heat can be transmitted to the body of the tissue penetrating probe from the applicator 28 in order to inhibit injury from the proximal portion of the probe in adjacent tissues of the skin. Other embodiments may apply a heated cryoprotective material above or below the surface of the skin.

[0058] In order to protect adjacent tissues from injury, it may also be advantageous to introduce the cooling fluid (such as liquid N2O) in thermal communication with the probe 26 in order to minimize excess flow over time. of treatment. The amount of liquid N2O or mass flow flowing in the needle probe may be a function of the fluid pressure from the fluid source 18, the inlet diameter of the fluid tube, an internal pressure inside the needle, and the quality of the N2O. The amount of liquid N2O desired to operate a needle probe may be a function of the desired temperature difference between the needle and the tissue, which may change over time. Extroversion of gas temperatures from the needle probe can change the quality of the incoming N2O flowing through the needle. Therefore, as a result of the dynamic flow requirements, it can be difficult to accurately enter only the desired amount of N2O.

[0059] Referring now to Fig. 3, a patch of cooling fluid 23 generally extends from the fluid supply 18 to the tissue penetrating probe 26 and from the probe to an exhaust (often by a valve of escape 25). A supply valve 27 will often be arranged along the fluid patch 23 to help control any condition of excess flow of the cooling fluid, the supply valve usually comprising a solenoid or other valve controlled by signals from a circuit controller 22. Controller 22 may also provide control signals for the exhaust valve 25 in response to the temperature or to cooling fluid pressure signals, usually in order to control the temperature of the probe 26 and / or the fluid pressure cooling of the former (or adjacent to it). Similarly, the controller 28 can also control the operation of the applicator 28, such that by varying the electrical energy supplied by a resistive heater in response to a temperature of the surface of the temperature measuring probe or a skin temperature involved or similar. The controller 22 can transmit signals to other applicators in order to control a flow of fluid from the applicator, for example, by activating a pump, by operating a valve, or the like.

[0060] To control any excess flow of cooling fluid in or through a probe 26, the supply valve 27 along the cooling fluid patch 23 between the fluid supply 18 and the probe 26 can be operated in pulses with in order to allow sufficient flow during the different parts of the treatment.

Table 1

EXAMPLE OF A 20 SECONDS TREATMENT

Weather

Position valve Duration

0-5 seconds

Open 5 seconds

5-7

Closed 2

7-11

Open 4

11-13

Closed 2

13-16

Open 3

16-18

Closed 2

18-20

Open 2

5 Table 1 shows an exemplary operating time for valve 27. During parts of the treatment when the valve is closed, the refrigerant can continue to flow through probe 26, although at a reduced pressure and at a correspondingly reduced flow rate. The pressure may decrease at a rate determined by the volume of the coupling valve of the refrigerant fluid patch 27 to the probe 26 (and / or to the tube 58 in Fig. 5B). As shown in this example, you can reduce the valve opening rate or time of

10 flow in the last stages of treatment (for example, after more than about 5 seconds of treatment) corresponding to the smallest desired flows. Different probes or arrays of probes having different numbers of probes, different lengths, and the like can be encoded mechanically or electronically to provide signals to controller 22 in order for the controller to provide adequate on / off programming (or other modulation) from valvule. Each individual probe can

15 be experimentally characterized to determine the proper programming of the valve in order to avoid excess flow conditions of the refrigerant.

[0061] Referring now to Fig. 3A, an alternative subdermal cryogenic remodeling system 40 includes a handpiece of the distal probe 42 coupled to a proximal controller housing 44 by a body

Flexible 20 46. The housing 44 includes a replaceable cooling fluid cartridge 48, again containing the exemplary liquid N2O cartridge and a connector for electric power 50. The housing 44 includes or also contains a user interface to accept inputs from the user of the system in a processor contained inside the housing, and for output parameters related to the state of the system, the progress of the treatment, tissue and / or treatment parameters, and the like.

[0062] Referring to Figs. 3A and 3B, the handpiece of the probe 42 generally extends distally from the body of the flexible probe 46 to a distal surface that is implanted in the tissue 52. A plurality of tissue penetrating needle probes 54 extend distally from the surface that is implanted in the tissue 52, the needle probes are cooled by a cryogenic cooling fluid that comes from the fluid source

30 48. The flexible body 46 may include a light 56 through which the vaporized cryogenic cooling fluid returns from the thermal contact with the probes 54 to the housing 44, with the housing 44, the handpiece 42,

or the flexible probe body 46 which includes a valve to regulate the pressure of the exhaust gases in order to control the treatment temperature under the direction of the processor inside the housing. A light may also be included for supplying the cooling fluid 58 within the flexible body 46 to transmit

35 the liquid cooling fluid to the probes 54. Electric power can be provided for the handpiece 42 from the housing 44 by the electrical conductors 60.

[0063] In the embodiment of Fig. 3B, the handpiece 42 includes an applicator in the form of a heated pad 62, the distal surface of the heating pad comprises the surface that is implanted in the fabric 52. In In general, the temperature of the surface of the probe that is implanted in the skin may be between about 37 ° C and about 90 ° C, with the surfaces of the heated probe that is implanted in the tissue at a temperature of about 45 ° C to about 90 ° C before contact with the skin, depending on the physical properties of the probe surface, such that the skin has a temperature of about 37 ° C to about 45 ° C during treatment. The surfaces of the probe formed on thermally conductive materials (for example, metals such as copper, aluminum, or the like) can be heated such that they have temperatures closer to 45 ° C before skin contact, while the materials do not Heat conductors (which often include polymeric materials such as silicone or a PTFE such as Teflon TM) can be heated to have temperatures closer to 90 ° C before contact. Other factors that can influence the temperature of the probe surface that is implanted in the skin prior to skin contact include the mass of the structure lining the probe, the location of the heater, and the like. Regardless of the initial temperature of the probe at the contact, the maximum desired temperature that the skin reaches can be approximately 45 ° C. To protect the skin and / or surrounding tissue, the probes described herein can be provided with applicators that apply thermal energy, materials, or the like, to inhibit injury along the surface of the skin or other tissue not directed by treatment

55 particular therapeutic.

[0064] The application of energy can heat collateral tissues near tissues directed for the application of cooling-based remodeling, such as to control temperatures on the internal and / or external surfaces of the skin, in the surrounding tissues. , or the like. This can be achieved with energy sources and / or by applying fluid with the controlled temperature. In Fig. 3B, the exemplary applicator comprises, for example, a heating pad 62 of stainless steel or the like. Heating of the applicator can be provided by a resistive heater structure powered by conductors 60 under the direction of the processor circuitry contained within the controller housing 44.

[0065] Together with the circuitry to control the heater of the probe surface that is implanted in the tissue, the processor circuitry inside the controller housing 44 will provide the on / off of the medium flow control for the N2O ( as well as a pressure regulation), a timer to apply and vary the heating, cooling, application of cryoprotectants or other materials, or the like. A wide variety of precooling inhibitor treatment regimens may be employed, during cooling, and / or after cooling the collateral tissue in order to allow the target tissues to cool, which are to be cooled to the desired treatment temperatures. during the desired treatment times with appropriate rates of change in temperature to provide the desired remodeling effect, while collateral tissues along the surface of the skin or the like are maintained at lesion inhibition temperatures .

[0066] Referring now to Fig. 3B and 3C, the cooling and structure of tissue penetrating probes 54 can be seen in more detail. Each probe again comprises a tube or needle 30 g with an external diameter of 0.012 inches (0.030 cm) having a sharp distal end 64. The temperature along the surface that is implanted in the skin 52 (and therefore, adjacent to the proximal end of the tissue penetrating probe 54) T1 may be hotter that the skin temperature, being normally hotter than 37 ° C, and in an exemplary embodiment being approximately 50 ° C. The distal portion of the tissue penetrating probe 54 for implanting a target tissue will have a temperature T4 which will be in general less than 10º C, often being 0º C or less, and being in many embodiments of -5º C or less, being in some embodiments of -15º C or less, or even of -25º C or less in order of providing sufficient volume d and tissue in the desired range of tissue temperature. The exemplary penetration needle 54 shown in Fig. 3C may have a distal portion 68 with a length of approximately 1 mm, optionally approximately 3 mm in length, and may be cooled to provide a treatment temperature to the external surface of the T4 probe of approximately -40º C.

[0067] A part of the cooling fluid directed to the handpiece 42 is transmitted along a light of the cooling fluid 58 inside the handpiece (from a manifold or the like, or optionally with each penetrating probe of the tissue having an associated lumen extending through a flexible body 46), with at least a part of the cooling fluid flowing as a liquid from an inlet of the cooling fluid inside the tissue penetrating probe 54 The cooling fluid is vaporized inside the probe 54, and the exhaust gases are vented proximally inside an handpiece 42, and then through the light 56 of the flexible body 46.

[0068] Even with reference to Fig. 3C, the distal portion 68 of the probe 54 will generally contain a mixture of cooling fluid in its liquid form with cooling fluid in its gaseous form. As the vaporization or boiling temperature of a fluid generally varies with pressure, if the pressure inside the distal portion 68 is relatively constant, the surface treatment temperature of the T4 probe along the portion Distal 68 will be relatively constant and can be controlled by varying the pressure inside the probe 54 and / or the handpiece 42.

[0069] The temperatures of the external surface of the probe T2, T3 between the distal portion 68 and the surface that is implanted in the skin 52 will normally be somewhat hotter than the treatment temperature of the T4 target tissue probe, particularly when the surface 52 that is implanted in the skin is heated. As the mixture of liquid and gas cooling fluid flows proximally into the tissue penetrating probe 54 and, the liquid can eventually vaporize completely allowing the gas to increase the temperature. Therefore, the external surface of the probe can gradually warm up as the operator moves it from the distal portion 68. Even if the liquid does not vaporize completely, heat can be transmitted from the heated pad 62 distally along the body of the probe. In the exemplary embodiment, the intermediate temperature T2 can be approximately 0 ° C, the temperature T3 being approximately -20 ° C.

[0070] Referring now to Figs. 4A and 4B, alternative mechanisms can also be provided to inhibit the lesion along the surface of the skin, including thermal insulation of at least a portion of the tissue penetrating probe or the surface that is implanted in the skin. of the handpiece of the probe. The tissue penetrating probe 54 here again comprises a 30 g stainless steel tube having an external diameter of approximately 0.012 inches (0.030 cm) and an internal diameter of approximately 0.006 inches (0.015 cm), with a closed distal end 80. Liquid N2O is introduced again through the light of the cooling fluid supply 58 with the vaporized gases escaping from the N2O 84 proximally through the internal light of the tissue penetrating probe 54. Optionally, the closed end 80 can limit the advance of the cooling fluid inside the tissue penetrating probe (54) in order to inhibit the cooling of collateral tissues disposed distally of the target tissues, the closed distal end optionally having a resistive heater, an insulating material, an electrode of tissue heating, a cryoprotective supply port, or some other distal tissue protection applicator.

[0071] In the embodiment of Fig. 4A, insulation 86 is provided between the cooling fluid flowing into the handpiece of the probe and the surface that is implanted in the skin 52 to protect the epidermis of the thermal coupling with any liquid N2O that flows excessively or similar. Additionally, an insulating layer or sleeve 88 disposed between an external surface of the probe 54 and the cooling fluid inside the probe 54 limits thermal cooling by means of the proximal cooling fluid of the distal portion that is implanted in the tissue target 68.

[0072] Optionally, direct cooling of the target tissue can be provided through the contact between the cooling fluid and the tissue, as illustrated in Fig. 4B. In this embodiment, a probe 90 has an open end 92. The liquid N2O 94 (or some other cryogenic cooling fluid) is directed from the light of the cooling fluid 58 to the open end 92, returning the gas back again. Vaporized exhaust 84 proximally.

[0073] When the probe 90 is inserted through the layers of epidermis 96 and dermis 98 such that the distal portion of the probe is within a target tissue 100, the surface that is implanted in the skin 52 of the handpiece of the probe is pushed firmly against the skin thus providing pressure to the dermal layers in the target tissue. Target tissue 100 is partially invaded in the lumen of the probe needle 90 blocking the closed distal end. The combined compression of the target tissue and the invagination contains N2O nitrous oxide (or other cooling fluid) inside the needle probe 90.

[0074] Referring now to Figs. 5A and 5B the handpiece of the alternative probe 110 has an applicator 112 that applies heating and a cryoprotective compound to the tissues disposed between the surface of the skin and the target tissues to inhibit damage to the collateral tissue.

[0075] The application of one or more cryoprotectant compounds (such as dimethyl sulfoxide, DMSO, and the like) to the internal and / or external surface of the skin, in the collateral tissue, or the like, with or without the heating of the compounds , can inhibit damage to collateral tissue. The handpiece of the probe 110 can also be used to inject heated biocompatible fluids such as saline in the dermal layers above the target tissue in order to inhibit damage to the collateral tissue. DMSO or other cryoprotective or biocompatible solvents may be applied to the epidermis and / or dermis before or during treatment. A variety of materials can be used, including DMSO propylene glycol cocktails and the like.

[0076] Solving the structure shown in Figs. 5A and 5B, the handpiece 110 includes an external housing 112 and an internal chamber defined by an internal housing 114, the internal housing optionally comprises (for example) a tube of stainless steel that has an external diameter of 0.14 inches (0.36 cm) and an internal diameter of 0.12 inches (0.30 cm). The external housing 112 partly defines an applicator for applying heat and a cryoprotective material to the dermal tissues, the internal and external housing together define a space between them for the passage of an infusion fluid from an inlet port 116 (such as a Luer accessory) for a plurality of infusion needles 118. In the exemplary embodiment, the outer housing 112 comprises a stainless steel pipe having an external diameter of 0.20 inches (0.51 cm) and a diameter internal of 0.18 inches (0.46 cm). A heater 120 is thermally coupled to the infusion fluid between the internal and external housings, the fluid infused by the infusion needles 118 is heated and the surface implanted in the skin 52 is provided at a temperature of approximately 45 ° C.

[0077] The cooling probes of the tissue penetrating needle 54 may comprise needles 30 g with the distal ends locked and having a length of approximately 3 mm. The fluid infusion needles 118 may comprise 30 g needles that are approximately 1.5 mm long. In general, the separation between the penetrating cooling treatment probes of the fabric 54 may be approximately between 1/4 mm and 2 mm, preferably having a needle-to-needle separation between approximately 1/2 mm and 1 mm, ideally being approximately 1/2 mm When fluid infusion needles 118 are provided, they can intermingle between at least some of the adjacent cooling treatment probes 54 and / or about a perimeter of the cooling treatment probes to limit the lateral spread of the cooling.

[0078] As illustrated in Fig. 5B, the distal portion of a handpiece of the multi-needle probe with saline solution or other fluid infusion can again have needle probes 54 extending through the dermis 98 and the epidermis 96 to a treatment zone, here in the hypodermis 130 Treatment zones can generally be defined by temperature profiles 132 in the cooled tissues adjacent to the distal portion of the needle probes by cryogenic cooling 54. The infused saline solution 134 in dermis 98 and / or epidermis 96 by infusion needles 118 can limit collateral lesion of these tissues between treatment areas 132 and skin surface 136.

[0079] As can be understood with reference to the temperature profiles illustrated in Fig. 5B, the treatment zones 132 can provide the desired temperatures in selected volumes or models of the target tissue, with adjacent regions of target tissue found by below or above target treatment temperatures. As can be understood with reference to Figs. 6A and 6B, the application of cooling from a cryogenic tissue penetration probe in which the cooling is applied principally or completely through the distal portion of the probe can also help to limit the injury of the tissues adjacent to the tissue. skin surface Advantageously, the temperature profiles can, to a significant extent, be determined by selecting the temperature of the probe surface, a cooling treatment time, a needle-needle separation, a probe and an isolation geometry, and the like.

[0080] Fig. 6A shows the isotherms of the tissues, as measured from the center of a tissue penetrating probe, after 60 seconds of exposure to cooling at -50 ° C surface temperature of the probe. Tissues along the surface of the skin reach a minimum temperature below 10º C and above 0º C. A similar graphical representation of tissue temperature isotherms after 10 seconds of exposure to cooling provides temperatures of the surface of the fabric above 20 ° C, as illustrated in Fig. 6B. The application of adequate energy or materials to collateral tissues is further adjusted to the shape of the tissue remodeling effect. Alternatively, damage to tissues along the skin surface and the like can be limited by effecting the desired cosmetic result using temperature ranges and / or times that inhibit damage to collateral tissues.

[0081] As indicated above, a variety of procedures can be used to protect the skin in the epidermal and / or endodermal layers. For example, a supply probe with multiple temperature zones can be used, the zones correspondingly corresponding to the materials of the probe and / or the insulation. In some embodiments the insulation (optionally segmented) can be developed in the delivery device; injection of saline solution or other heated biocompatible fluid may be provided; injection of a biocompatible cryoprotectant can be provided; and / or the application of energy can be provided to limit damage to collateral tissue.

[0082] Other alternative mechanisms can be used to limit damage to collateral tissue, optionally enhancing the effects of cooling or other remodeling on target tissues. In some embodiments, it may be advantageous to enhance subtermal ice formation and / or heat conduction. The fat has insulating properties, and the saline solution can be 3x as conductive as the fat, such that adding saline solution (or other conductive agents) can help freeze some target tissues, including adipose tissues. Therefore the injection of saline solution or some other material can enhance thermal conductivity and remodeling efficiency of cooling and / or control of the target region. Injection of such materials to disseminate the efficacy of remodeling through a wider anatomical region may be particularly desirable. The cooling front can preferably travel through the saline solution Below 0 ° C or by solidifying the saline solution, the saline solution can be approximately three times as heat conductive as fatty tissues. Injection or other application of compounds may also enhance the desired tissue remodeling by other mechanisms. For example, the application of hypertonic solutions such as saline solution having sufficient salinity can enhance the effects of cold or heat on target tissues by altering the size of the cells, dehydrating the cells, and / or the like. In some embodiments, the application of said hypertonic solutions can effect the desired remodeling of the target tissues without the application of cold or heat.

[0083] Inhibition of muscle function can be used permanently and / or temporarily. A temporary effect can be used on a clinical trial basis to avoid long-term injuries or other undesirable outcomes. A permanent effect may be desirable to minimize cost and to avoid repeated treatments the desired temperature ranges to temporarily and / or permanently disrupt the muscle, as well as to protect the skin and surrounding tissues, may be indicated in Table 2. as follows:

Table 2

Temperature

Skin Muscle / fat

37º C

Initial value Initial value

25º C

Feeling cold

18º C

Reflex vasodilation of deep blood vessels

15º C

Painful cold feeling

12º C

Spasticity Reduction

10º C

Very cold sensation Reduction of chronic edema Response search

5th C

Sensation of pain

0º C

Freezing point

-1º C

The transition phase begins

-2º C

minimal apoptosis

-3º C

Transition to the peak phase

-5º C

Tissue damage moderate apoptosis

-8º C

Exhaustion of the phase transition

-10º C

considerable apoptosis

-15º C

Mild-moderate necrosis with extensive apoptosis

-40º C

Extensive necrosis

[0084] To overcome the potential of an undesirable outcome, treatments can be administered in a controlled manner, a little at a time during the course of various procedures. When the muscle is

5 affected, a temporary loss of elasticity can be observed through changes in the morphology of collagen and elastin at the beginning of ice formation. The degree to which there is a loss of movement is likely to increase a larger percentage of cells that are affected. This can be controlled by varying the treatment parameters such as times, rates, and temperatures. At the lowest temperature, the highest percentage of cells is the one that experiences the effect of inhibition of contraction.

[0085] In light of the foregoing, and in order to provide cosmetic tissue remodeling with a desired or selected duration of efficacy, tissue treatment temperatures for the Table may be employed as follows:

15 Table 3

Cold temperature range

Time efficiency objective

� 00 C

The treatment lasts only while the needle is inserted into the target tissue. It can be used to identify target tissues.

From 0º C to -5º C

It often lasts for days or weeks, and the target tissue can repair itself. The realizations can last hours or days. Temporary treatment It can be used to evaluate the effectiveness of the remodeling treatment on the superficial shape of the skin or the like.

From -5º C to -15º C

It often lasts months to years; And it can be permanent. Limited muscle repair. The accomplishments can last weeks to months. Potential permanent long-term cosmetic benefits. They can be deployed in limited doses over time to achieve a staged impact, controlling the result and avoiding the negative result. It can be used as a standardized treatment.

From -15º C to -25º C

It often lasts weeks or months. The muscle can repair itself by mobilizing satellite cells. The accomplishments can last for years. It can result in medium-term cosmetic benefits, and can be used when permanent effects are not desired or to evaluate the results of potentially permanent dosing the embodiments may provide permanent treatment.

[0086] As can be understood with reference to Figs. 5B, 6A, and 6B, some tissues can be exposed to temperatures above or below the desired temperature range, and variation of

effects on tissues, particularly some necrosis when lower temperatures are used.

[0087] There is also a temperature window in which apoptosis can be induced. An apoptotic effect can be temporary, long-term (lasts at least weeks, months, or years) or even permanent. Although the necrotic effects can be long-term or even permanent, apoptosis can actually provide more long-term lasting cosmetic benefits than necrosis. Apoptosis can present a non-inflammatory cell death. Without inflammation, normal muscle healing processes can be inhibited. After many muscle injuries (which include many injuries that involve necrosis), the skeletal muscle satellite cells can be mobilized by inflammation. Without inflammation, this mobilization can be limited or avoided. Apoptotic cell death can reduce muscle mass and / or can disrupt the connective chain of collagen and elastin. The temperature ranges that generate a mixture of these apoptosis and necrosis can also provide long-term or permanent lasting results.

[0088] Apoptosis, alternatively called "programmed cell death," is a mechanism of self-destruction directed at genes by which cells die without adversely affecting the surrounding tissues. It is characterized by a well-ordered sequence of events, including chromatin condensation, nuclear fragmentation, and vesicle formation in the membrane. Apoptosis plays numerous roles in the development and regulation of healthy tissue. As part of the development and differentiation of normal tissue, apoptosis is part of a strategy to select some cells for survival, thus sculpting tissue specificity. In mature tissue, cell division balances apoptosis to prevent excess tissue growth.

[0089] Another role of apoptosis is to ensure that injured or mutated cells do not proliferate. Environmental or psychological stimuli with cell damage can induce or activate the generic apoptosis program specifically, harmful external stimuli (such as exposure to cold) can activate the genes that drive the apoptotic cascade of events. Apoptosis can be stimulated by a physiological stimulus that is not in itself harmful and that causes death to only a specific population of cells and various forms and various forms of cell injury, both induced by immune effector cells, abnormal metabolic processes, drugs Chemotherapeutic or temperature changes, which can result in common morphological changes that include the formation and shedding of membrane vesicles from injured cell surfaces, and / or apoptosis.

[0090] In other words, normal cells can be genetically programmed with a suicidal routine, which leads to the term "programmed cell death." This programming can be activated or stimulated by exposure to non-lethal cold. Alternative mechanisms can also be used to stimulate apoptosis including adequate exposure to chemical agents or heat as well as stress induced by hypoxia due to loss of vascular perfusion. Therefore, cryotreatments and other procedures can be accurately described as inducers or stimulators of apoptosis.

[0091] For the reduction of adipose tissue, a permanent effect may be advantageous. Surprisingly, apoptosis and necrosis can produce long-term or even permanent results in adipose tissues, because fat cells regenerate differently than muscle cells.

[0092] Aspects of healing that may be useful for these treatments include the four phases of healing; inflammation (immediate); substrate (6 hours); repair (5-6 days), and maturation. The return of at least some muscle resistance in normal healing usually occurs in 4-6 days after the injury and may take 14-16 days. The formation of scars in the tendons can cause lengthening, thereby inhibiting contractions of an associated muscle. In addition, specifically the separation lesion can result in the growth of new tissue to reconnect, resulting in an increase in length and a loss of contractability (and therefore a flaccid muscle). Healing can occur through fibrosis and the regeneration of myofibrils. Scar tissue can strangle myofibrils, preventing regeneration. Between muscle endings, scar tissue may lengthen resulting in poor contractability. Similarly, any break in the connective tissue chain can inhibit contractions including in a ligament or tendon. The ligaments may have a capacity to reform, closely approaching the structure of the original pretreatment. Likewise, the tendon, if the extremes (of serious injuries) cannot heal together, can cause elongation leaving them weak. Lesions that are not serious may effectively be similar to sutured rupture that does not lengthen.

[0093] Referring now to Figs. 7A and 7B a more additional alternative system may include a proximal controller housing 140 and / or a handpiece of the probe applicator 142 as schematically illustrated. In this embodiment, the controller housing 144 includes a receptacle for a cooling fluid cartridge 48 with the cooling fluid being the cartridge replaceable and having sufficient cooling fluid for at least a significant portion of a single patient treatment. The user interface of the controller housing 144 includes a selector and / or indicator of the treatment time 146 and an indicator 148 which can generally indicate the type of treatment or characteristics such as the treatment temperature, the duration of the treatment effectiveness , or the like.

[0094] The flexible body 46 extending between the housing of the controller 144 and the handpiece of the probe 142 includes a light for the supply of the cooling fluid 58, together with a feedback of the thermal coupling 150 a conductor of the switch on / off the power supply of heater 152, and the like. The handpiece 142 includes a start button 154, and includes a proximal housing 156 and a replaceable distal body 158. The body 158 includes a needle array 60 as described above, and is detachably coupled to a body proximal 156 and to a source of saline solution or other infusion of fluid

162. The fluid source 162 may comprise a pump, syringe, drip system, or the like and may provide a saline solution, a cryoprotectant, another biocompatible fluid, or the like. The hot fluid can be supplied from the fluid source 162 or it can be heated in / or an adjacent body 158.

[0095] Referring now to Figs. 8A-8C, a plurality of bodies or heads of handpieces of the probe of different configurations can be provided. The head of the probe 170 includes an array of probes

or tissue penetrating needles 54 that are arranged to produce a volume of treatment. A thermal sensor 172 on the surface that is implanted in the skin 52 controls the temperature of the skin, and can be used to control a heater of the probe skin and / or the cooling treatment.

[0096] An alternative probe head 174 shown in Fig. 8B includes long tissue penetrating probes 54 arranged in a linear array 176, and facilitates treatments along a plane, such as parallel to a bone. A more additional alternative probe head 178 similarly includes a needle matrix 180 at intervals to produce a surface treatment in a plane or line. A probe head base 182 may be rigid (being formed, for example, of stainless steel) or it may be flexible to conform to the surface of the skin or tissue that is implanted in the skin (i.e., silicon). Resistive heating elements can be provided within the base of the probe head, whether it is rigid or flexible. For example, a resistive heating element inside a silicon probe head base having approximately 2.5 watts per square inch (6.45 cm2) of surface area can produce surface temperatures of approximately 45 ° C, suitable for warming the surface of the skin.

[0097] Referring now to Fig. 9, an embodiment of a method 200 for performing a cosmetic treatment 200 includes the identification of a cosmetic defect 202 such as wrinkles, grooves, cellulite, fat, or the like. A desired restoration of the skin surface 204 is determined which may include the removal of wrinkles or furrows, softening cellulite dimples, fat reduction, or the like. In many embodiments, it may be desirable to avoid permanently altering the color. of the skin surface when performing such treatments.

[0098] An appropriate target tissue 206 is identified, such that a nerve, muscle, a neuromuscular junction, connective tissue, a layer of adipose tissue, or the like below the cosmetic defect is identified. A duration of the remodeling effect 208 can be selected, and the treatment probe 210 placed. The location of the treatment probe may, for example, comprise inserting one or more needles of the tissue penetrating probe into the target tissue, which is implanted on the surface of the skin with a surface that is implanted in the skin of a handpiece, and / or the like. The skin lesion 212 can be inhibited, such that the surface of the skin is heated, infusing a heated biocompatible fluid such as a saline solution, applying a cryoprotectant such as DMSO, or the like.

[0099] Cooling and / or energy (or chemical or vascular embolization) is applied to target tissue 214 in order to effect the desired remodeling of this tissue. The response and healing of tissue 216 can follow immediately after cooling and / or energy (or chemical or vascular embolization) is applied, or it can take place in a considerable time (such as when efficiency is achieved through apoptosis or similar) If a short duration of the test treatment has been carried out to verify the target tissue and the effect of the treatment, a retreat can be carried out 218.

[0100] Although exemplary embodiments have been described in some detail to improve clarity and understanding and by way of examples, numerous modifications, changes, and adaptations can be implemented and / or will be obvious to those skilled in the art. For example, one or more temperature feedback loops can be used to control the treatments, the temperature of the tissue being optionally taken at varying tissue levels using (for example) the plurality of advanced thermal couplings at varying tissue depths using a needle temperature sensitive Therefore, the scope of the invention is limited only by the independent claims.

Claims (15)

1. A system for cosmetically restoring an exposed skin surface of a patient, the system comprising: a body having at least one cooling fluid supply patch (23), in which the body comprises a handpiece (42); a probe (26) that is in thermal communication with said cooling fluid supply patch and that extends distally from the body, the probe comprising a probe body (158, 170, 174) that includes a matrix of penetrating needles of the tissue (54), each needle extending distally from the probe body and comprising a sharp, sealed or blocked distal end inserted into a patient's target tissue across the skin surface; wherein the inner light of the respective needle is configured to receive a cooling fluid from the outlet (70) of a cooling fluid light (58) disposed inside the handpiece (42); a source of cooling fluid (48) coupled to the at least one patch of cooling fluid supply (23) of the body to cool the tissue penetrating needles (54) distally of the probe body in order to reshape the adjacent tissue and temporarily inhibit the contraction of a subdermal muscle and reduce the appearance of wrinkles and grooves on the side associated with muscle contraction; Y, proximally of the distal ends of the needles (54), an applicator (62, 118) of the probe to apply energy or a material in order to inhibit the injury induced by cooling along the surface of the skin.

2.

The system of claim 1, further comprising a controller (22) coupled to the cooling fluid patch (23) in order to control at least one of a treatment time or a treatment temperature.

3.

The system of claim 2, wherein the controller is configured to provide a treatment temperature between about 10 ° C and -50 ° C, optionally a treatment temperature between about 0 ° C and -15 ° C.

Four.

The system of claim 2, further comprising an input to identify a desired duration of remodeling, wherein the controller (22) determines a cooling characteristic comprising a temperature, time, temperature change rate in response to the desired duration

5.

The system of claim 1, wherein the probe body (158) has a surface that is implanted in the skin (52) adjacent to a proximal end of the needles (54)

6.

The system of claim 5 wherein a separation between the needles (54) of the die is arranged to cool the tissues disposed therebetween.

7.

The system of claim 5 or 6 wherein the needles (54) have a distal cooling region of the surface that is implanted in the skin (52), a plurality of cooling fluid patches being terminally coupled to the regions of cooling to selectively cool a target tissue adjacent to the previous one, and in which the applicator is proximal to the cooling regions to apply the energy of the material in order to inhibit the injury induced by cooling along the surface of the skin.

8.

The system of claim 5 or 6 wherein the applicator (62, 118) is configured to direct the heated biocompatible fluid or biocompatible cryoprotectant adjacent to the skin surface in order to inhibit skin surface injury .

9.

The system of claim 5 or 6 wherein the needles (54) have a region of distal cooling of the surface that is implanted in the skin to selectively cool the target tissue, and an isolated region (88) disposed between the region of cooling and the surface that is implanted in the skin (52) in order to inhibit the lesion along the skin surface.

10.

The system of claim 5 or 6 wherein the needles (54) have a distal cooling region of the surface that is implanted in the skin (52) to selectively cool the target tissue, and wherein the applicator is close to the cooling regions to apply the material to enhance the cooling of the target tissue.

eleven.

The system of claim 1, wherein the source of cooling fluid (18) comprises a single-use cartridge or a refillable cartridge (48) having a quantity of the cooling fluid.

12.

The system of claim 11, further comprising a system housing (16) comprising a controller (22) in which the single-use or refillable cartridge (48) and the probe are supported

by the system housing (16), the system housing containing a patch of cooling fluid that couples the cartridge (48) to the probe, and the controller (22) coupled to the cooling fluid patch of the system housing with the in order to control the cooling fluid, in which the system housing is disposable. The system of claim 1, wherein the applicator (62, 118) comprises a resistive heater or an isolated region between a coding region and a surface that is implanted in the skin of the probe body. 14. The system of claim 1, further comprising infusion needles (118), wherein the part Handheld 10 includes an external housing (112) and an internal chamber defined by an internal housing (114), the internal and external housing jointly defining a space between them for the passage of an infusion fluid from an inlet port (116) ) to a plurality of infusion needles (118). 15. The system of claim 14, wherein a heater (120) is thermally coupled with the 15 Infusion fluid between the internal and external housings (112, 114) to heat the fluid infused by the infusion needles (118) and to provide a surface that is implanted in the skin (52) at a temperature of approximately 45 ° C. 16. The system of claim 14 or 15, wherein the infusion needles (118) are intermingled 20 between at least some of the penetrating needles of the adjacent tissue (54) and / or about a perimeter of the penetrating needles of the tissue (54) to limit the lateral spread of the cooling.